Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

PMID:31941401

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy.

Identified Atg38 as a subunit of the PtdIns3K complex I in S. pombe

"We showed that it is an important member of the PtdIns3K complex I"
Discovered the AIM motif in Atg38 that mediates direct interaction with Atg8

"Sequence conservation among 4 fission yeast species led to our discovery of an AIM in S. pombe Atg38"
Demonstrated that Atg38-Atg8 interaction establishes a positive feedback loop for autophagy

"We revealed that the Atg38-Atg8 interaction establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to facilitate autophagosome formation"
Showed that atg38 deletion abolishes nitrogen starvation-induced autophagy

"in atg38Δ cells, no elevation of Pho8Δ60 activity was observed"
Characterized Atg38 localization to the phagophore assembly site

"The Atg38-Atg8 interaction promotes PAS accumulation of Atg38"

Visual detection of binary, ternary and quaternary protein interactions in fission yeast using a Pil1 co-tethering assay.

Demonstrated Atg38-Vps34 interaction using Pil1 co-tethering assay

"Atg38 is incorporated into the PtdIns3K complex I via an Atg38-Vps34 interaction"
Confirmed Atg38 incorporation into PtdIns3K complex I

"Atg38 is incorporated into the PtdIns3K complex I via an Atg38-Vps34 interaction"

file:SCHPO/atg38/atg38-deep-research-perplexity.md

Deep research review of atg38 gene function

Comprehensive review of Atg38 structure, function, and localization
Clarified that mug167 naming does not indicate meiosis-specific function
Described the positive feedback loop mechanism between Atg38-Atg8

file:SCHPO/atg38/atg38-deep-research-falcon.md

Falcon (Edison) deep research synthesis of atg38 (O94427) function

Atg38 is a non-enzymatic autophagy factor acting as an accessory/scaffolding/regulatory subunit of the PtdIns3K complex I at the PAS/phagophore, not an enzyme.

"Atg38 (SPBC660.08; Mug167) is a **non-enzymatic autophagy factor** that acts as a **PtdIns3K/PI3K complex I subunit** at the **PAS/phagophore**"
Atg38 is best understood as an accessory/scaffolding/regulatory subunit of the autophagy-initiating PI3K complex rather than as an enzyme.

"Atg38 is therefore best understood as an **accessory/scaffolding/regulatory subunit** of the autophagy-initiating PI3K complex rather than as an enzyme itself"
Atg38-family proteins have a conserved MIT + coiled-coil/homodimerization architecture supporting complex association and punctate localization.

"Atg38-family proteins have a conserved **MIT + coiled-coil/homodimerization** architecture that supports complex association and punctate localization"
In S. pombe, Atg38 is incorporated into PI3K complex I via direct binding to Vps34, a species-specific feature; the interface centers on Atg38 F157 and Vps34 residues 251-801.

"Vps34 residues **251–801** (helical + lipid kinase domain region) mediate binding to Atg38, whereas Vps34 residues **1–250** mediate Vps15 binding"
Atg38 directly binds Atg8 via an AIM (around aa 173-185; key residues F178 and V181), creating a positive-feedback loop that amplifies PAS accumulation of complex I.

"supporting a model in which Atg38–Atg8 binding amplifies PI3K complex I presence and downstream assembly at the PAS"
Loss of Atg38 or disruption of its Atg8 AIM reduces autophagic flux and yields smaller autophagosomes (451 nm WT vs 271 nm AIM mutant in an fsc1delta TEM context).

"mean autophagosome diameter was **451 nm** (WT Atg38 condition) versus **271 nm** in cells expressing **Atg38[AIM mut]**"